A 2‐Year‐Old Girl with Dysmetria and Ataxia

Clinical History

A 2‐year‐old girl presented with 1‐month history of dysmetria and ataxia. Computer tomography (CT) of the brain showed a large parietal‐occipital mass and marked hydrocephalus, for which she required placement of bilateral ventriculoperitoneal shunts. Magnetic resonance imaging (MRI) of the brain also revealed two nodules within the lateral ventricle (Figure 1A). Spine MRI showed abnormal leptomeningeal enhancement along the cervical spine, with additional enhancement in the thoracic and upper lumbar spine. A metastatic origin was excluded by exhaustive radiologic investigations, including body CT and positron emission tomography. Her disease progressed following completion of 6 months of intravenous and 3 months of oral chemotherapy; MRI showed interval increase in the size of the left temporal lobe ventricular lesions as well as worsening leptomeningeal disease and new parenchymal nodules. The tumor was completely excised.

Figure 1.

 

Microscopic Pathology

Low magnification microscopy (×4) of H&E staining of the tumor displayed a variable architecture consisting of solid sheets, islands (×10, Figure 1B) and interconnecting cords of cells set in a vascularized fibromyxoid stroma (×10, Figure 1C) interspersed with areas of necrosis and calcification. Ductal differentiation was identified in rare foci within <10% of the tumor mass (×40 Figure 1D). The cells were polymorphic with round to oval, occasionally spindle‐shaped nuclei, conspicuous nucleoli and moderate cytoplasm (×20 Figure 1E). Mitotic figures were readily identified (×40, Figure 1F) with a high level of immunolabeling with Ki‐67/MIB‐1 immunostain.

The cells demonstrated a divergent immunophenotype with immunoreactivities for S‐100 (Figure 1G), smooth muscle actin (Figure 1H), CAM 5.2 (Figure 1I) and EMA (Figure 1J ×40). Retained immunoreactivity with BAF‐47/INI1 (×40, Figure 1K) and BRG‐1 were retained within the tumor cells. The cells were immunonegative for GFAP (×40, Figure 1L), pleomorphic adenoma gene 1 (PLAG‐1) and germ cell markers including placental alkaline phosphatase (PLAP), Oct 3/4, alpha‐feto protein (AFP) and CD30. EWSR1 gene rearrangement was not identified by fluorescent in‐situ hybridization. What is your diagnosis?

Final Diagnosis

Malignant myoepithelioma with extensive leptomeningeal spread to the cervical, thoracic and lumbar spine.

DISCUSSION

Tumors with myoepithelial differentiation occurring either as dura‐based lesions or within the central nervous system (CNS) are exceedingly rare, and as such, seldom considered in the spectrum of differential diagnoses for intracranial/dura‐based lesions. These tumors, however, are increasingly recognized at sites other than the major and minor salivary glands, including breast, skin, lung and soft tissue. Malignant cases of myoepithelioma have been described in the lacrimal gland, tongue base, nasal cavity, maxillary sinus, nasopharynx, larynx and vulva 2, 4. Literature review reveals only one other similar case presenting in an adult woman 3 and a recent report of its occurrence in the skull bone 3.

Myoepithelial lesions in the salivary gland include pleomorphic adenomas (benign mixed tumors), myoepitheliomas, carcinoma ex‐pleomorphic adenomas and myoepithelial carcinomas. Significant morphologic overlap between myoepitheliomas and benign mixed tumors suggests they lie along a morphologic continuum. The tumor in the present case was composed of neoplastic cells exhibiting morphological variation ranging from epithelioid, spindled, polygonal and plasmacytoid. The cells were arranged in cords, small nests and diffuse sheets set in a variably fibromyxoid matrix. Ductal differentiation within the tumor comprised less than 10% of the entire lesion, which favors the diagnosis of myoepithelioma 1 as opposed to a mixed tumor. The diagnostic dilemma to classify this tumor at the initial histopathological examination illustrates the difficulties often encountered in accurately classifying many of the high‐grade childhood brain tumors. The tumor morphology was unusual that did not readily fit into the well‐recognized WHO classification of CNS tumors and the lesion was originally categorized as a high‐grade, small‐round cell tumor with epithelial differentiation. Immunoreactivities for S‐100 protein and both epithelial and muscle markers combined with the morphological features of a neoplasm of myoepithelial histogenesis, prompted a diagnosis of malignant myoepithelioma.

Hemangiopericytoma and synovial sarcoma are recognized dural neoplasms that share morphologic similarities. Immunohistochemical positivity for the combination of cytokeratin, EMA, S‐100 protein and SMA, however, excludes hemangiopericytoma and synovial sarcoma as two possibilities. IR for cytokeratin, S‐100, EMA, SMA and GFAP add a number of other neoplasms to the differential diagnosis, including rare morphologic variants of meningioma which are all recognized dural neoplasms. Expression of SMARCB1 and SMARCA4 gene products (BAF‐47/INI‐1 and BRG‐1, respectively) by tumor cells helps in differentiating this tumor from the more common high‐grade childhood tumor‐atypical teratoid rhabdoid tumor. Exhaustive radiological investigations excluded the possibility of an intracranial metastatic lesion. Rare tumors like germ cell neoplasms were excluded immunohistochemically.

The occurrence of salivary gland rests within normal pituitary and the sellar region may explain the intracranial location for some of these tumors; but it does not explain the occurrence of malignant myoepithelioma within the parietal lobe or attached to the dura. The “multipotent stem cell” is proposed to be the likely cell of origin at these sites 2. The biological behavior of malignant myoepithelioma exhibits a diverse pattern similar to its varied cytoarchitectural spectrum and no specific clinical or morphologic features can be attributed to correlate with local recurrence. Rarely, tumors with benign features have been found to exhibit local recurrence.

While intracranial neoplasms of myoepithelial origin have been recognized in the suprasellar region arising from salivary gland rests within the pituitary gland, rare single reports of such a tumor in the meninges and skull bone exists in the literature to date 2, 3. This case highlights the importance of considering this tumor in the differential diagnosis of nonmeningothelial meningeal tumors with epithelioid and spindle‐cell morphology. The current lack of data regarding this entity makes it difficult to determine the best therapy and potential outcomes for affected patients. Significant cytologic atypia and frequent mitoses in the setting of extensive leptomeningeal spread portend a poor prognosis for the present case; however, the child remains clinically well 30 months from diagnosis after five cycles of salvage chemotherapy and most recently irradiation for progressive disease on neuroimaging.